Impact of TGF-ß1 -509C/T and 869T/C polymorphisms on glioma risk and patient prognosis

Transforming growth factor beta (TGF-ß) plays an important role in carcinogenesis. Two polymorphisms in the TGF-ß1 gene (-509C/T and 869T/C) were described to influence susceptibility to gastric and breast cancers. The 869T/C polymorphism was also associated with overall survival in breast cancer patients. In the present study, we investigated the relevance of these TGF-ß1 polymorphism in glioma risk and prognosis. A case-control study that included 114 glioma patients and 138 cancer-free controls was performed. Single nucleotide polymorphisms (SNPs) were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95 % confidence intervals (95 % CI). The influence of TGF-ß1 -509C/T and 869T/C polymorphisms on glioma patient survival was evaluated by a Cox regression model adjusted for patients' age and sex and represented in Kaplan-Meier curves. Our results demonstrated that TGF-ß1 gene polymorphisms -509C/T and 869T/C are not significantly associated with glioma risk. Survival analyses showed that the homozygous -509TT genotype associates with longer overall survival of glioblastoma (GBM) patients when compared with patients carrying CC + CT genotypes (OR, 2.41; 95 % CI, 1.06-5.50; p = 0.036). In addition, the homozygous 869CC genotype is associated with increased overall survival of GBM patients when compared with 869TT + TC genotypes (OR, 2.62; 95 % CI, 1.11-6.17; p = 0.027). In conclusion, this study suggests that TGF-ß1 -509C/T and 869T/C polymorphisms are not significantly associated with risk for developing gliomas but may be relevant prognostic biomarkers in GBM patients.This work was supported by Fundação para a Ciência e Tecnologia, Portugal (PTDC/SAU-GMG/113795/2009 and SFRH/BPD/33612/2009 to B.M.C.; SFRH/BD/88121/2012 to J.V.C.; SFRH/BD/92786/2013 to C.S.G.; PTDC/SAU-ONC/115513/2009 to R.R.)

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

Publisher Correction: Brain charts for the human lifespan

In the version of this article initially published, there were errors in the affiliations for K. Im (missing affiliation, Division of Newborn Medicine and Neuroradiology, Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA), J. Lerch (missing affiliation, Mouse Imaging Centre, Toronto, Ontario, Canada), S. Villeneuve and X. N. Zuo (incorrect affiliation numbers listed), H. Yun (missing affiliation, Division of Newborn Medicine and Neuroradiology, Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA), and H. J. Zar (extra affiliation shown). In addition, the affiliation numbers for all authors listed in the consortium membership section were incorrect by 1–3 digits. The errors have been corrected in the HTML and PDF versions of the article

Valorisation of Biowastes for the Production of Green Materials Using Chemical Methods

With crude oil reserves dwindling, the hunt for a sustainable alternative feedstock for fuels and materials for our society continues to expand. The biorefinery concept has enjoyed both a surge in popularity and also vocal opposition to the idea of diverting food-grade land and crops for this purpose. The idea of using the inevitable wastes arising from biomass processing, particularly farming and food production, is, therefore, gaining more attention as the feedstock for the biorefinery. For the three main components of biomass—carbohydrates, lipids, and proteins—there are long-established processes for using some of these by-products. However, the recent advances in chemical technologies are expanding both the feedstocks available for processing and the products that be obtained. Herein, this review presents some of the more recent developments in processing these molecules for green materials, as well as case studies that bring these technologies and materials together into final products for applied usage

Abstract P1-01-16: Intraoperatively-palpable “non-sentinel” nodes: should they be removed?

Abstract Background: Sentinel lymphadenectomy is the standard of care for evaluation of the axilla in breast cancer. Not infrequently, despite a clinically negative axilla, axillary nodes are found and removed that are only palpable intraoperatively at the time of sentinel lymph node biopsy. There is limited data suggesting that their resection is beneficial, and there is some controversy over whether these non-hot, non-blue nodes should also be called “sentinel nodes” (SNs). Methods: A retrospective chart review was conducted of breast cancer patients who underwent sentinel lymph node biopsy from 2007 to 2011 at a single institution. Patients were only included if they had SNs removed (defined as blue and/or radioactive nodes), as well as additional non-sentinel nodes that were only palpable intraoperatively (pNSNs) and not part of an axillary dissection (ALND). Pathology of both SNs and pNSNs were reviewed. Histologic nodal evaluation was performed by H&amp;E alone. Results: From 2007 to 2011, a total of 59 patients had both SNs and pNSNs removed. Fifty-five patients (93.2%) were female and the average age was 55 years old. Fifty-two patients (88.1%) had invasive ductal carcinoma while 7 had lobular carcinoma (11.9%). Average tumor size was 2.0 cm. Among the 59 patients, a total of 109 SNs (mean 1.8, median 1, range 1–6) and 202 pNSNs (mean 3.4, median 2, range 1–30) were removed at the same surgery. Twenty patients (33.9%) had metastases in either the SNs and/or pNSNs with 16 (80.0%) of these having metastases in the SNs alone. Sixteen patients proceeded to an ALND. There were 4 patients (6.8%, 95% CI 1.9–16.5%) who had SNs negative for tumor but pNSNs positive for tumor, and 4 (6.8%, 95% CI 1.9–16.5%) separate patients who had extracapsular extension (ECE) in their pNSNs but no ECE in the SNs. The pNSNs thus provided information altering operative treatment by American College of Surgeons Oncology Group (ACOSOG) Z0011 trial criteria in 8 patients (13.6%). Two patients (3.4%, 95% CI 0.4–11.7%) had ECE present in ALND nodes, but not present in either their SNs or pNSNs. Conclusion: pNSNs provide information that changes the surgical plan by ACOSOG Z0011 criteria in 14% of cases. Whether their removal changes patient outcomes remains unclear, especially as SNs and pNSNs may, together, be falsely-negative for ECE present within the axilla. While we recommend their removal at this time based upon the added information they provide, further study is required to determine whether the changes resulting from pNSN dissection (i.e. need for ALND) provide any outcome benefit in this era of effective systemic therapy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-16.</jats:p

IL-10 and TNF-α polymorphisms and the recovery from HCV infection

Hepatitis C virus (HCV) infection becomes chronic in about 85% of infected individuals, whereas only 15% of infected people clear spontaneously the virus. It is conceivable that the host immunogenetic background influences the course of infection in term of recovery. Thus, in this study we have evaluated the effect of functionally relevant polymorphisms at tumor necrosis factor-α (TNFα, i.e., 2 biallelic polymorphisms at nt -863 and nt-308 of the promoter) and interleukin-10 (IL-10) loci (i.e., 1 biallelic polymorphism at nt -1082 of the promoter), on the clearance of HCV infection. To this purpose, we compared 18 Sicilian patients who had spontaneously recovered from previous HCV infection with 42 Sicilian patients with current HCV infection and 135 Sicilian healthy patients. The results demonstrate a decreased frequency of the -863CC TNF-α promoter genotype (involved in high production of this pro-inflammatory cytokine) and an increased frequency of the -1082GG IL-10 promoter genotype (involved in high production of this anti-inflammatory cytokine) in patients recovered from HCV infection. The evaluation of combined TNF-α and IL-10 genotypes revealed a significant increase of the “anti-inflammatory genotype” (low-TNF/high-IL-10 producers) in resolved HCV infection group compared with patients with persistent HCV infection. On the whole, our findings suggest that a genetically determined control of the HCV-induced inflammatory response may play a role in the resolution of HCV infectio